Ly Annie, Karnosky Rachel, Prévost Emily D, Hotchkiss Hayden, Pelletier Julianne M, Spencer Robert L, Ford Christopher P, Root David H
Department of Psychology and Neuroscience, University of Colorado Boulder, 2860 Wilderness Pl, Boulder, CO, 80301, USA.
Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, 80045, USA.
Mol Metab. 2025 Jun 6;98:102178. doi: 10.1016/j.molmet.2025.102178.
The bed nucleus of the stria terminalis (BNST) is involved in feeding, reward, aversion, and anxiety-like behavior. We identify BNST neurons defined by the expression of vesicular glutamate transporter 3, VGluT3.
A combination of in situ hybridization, tract tracing, ex vivo whole-cell electrophysiology, in vivo recording, optogenetic, and behavioral approaches were used.
VGluT3 neurons were localized to anteromedial BNST, were molecularly distinct from accumbal VGluT3 neurons, and co-express vesicular GABA transporter (VGaT). BNST VGluT3 neurons projected to arcuate nucleus (ARC) and paraventricular nucleus of the hypothalamus (PVN), regions critical for feeding and homeostatic regulation. Most single BNST VGluT3 neurons projected to either PVN or ARC and a subset projected to both. BNST VGluT3 neurons functionally transmit GABA to both ARC and PVN, with rare glutamate co-transmission to ARC. In vivo, VGluT3 BNST neurons showed greater neuronal activity in response to sucrose consumption while sated compared with fasted. When fasted, optogenetic stimulation of BNST VGluT3 neurons decreased sucrose consumption using several stimulation conditions but not when stimulation occurred prior to sucrose access, suggesting that BNST VGluT3 activation concurrent with consumption in the fasted state reduces feeding. BNST VGluT3 activation had no effect on anxiety-like behavior in several paradigms (novelty-suppressed feeding, open field, and elevated zero maze). BNST VGluT3 activation also did not result in real-time place preference or aversion.
We interpret these data such that VGluT3 BNST neurons represent a unique cellular population within the BNST that provides inhibitory input to hypothalamic regions to decrease sucrose consumption.
终纹床核（BNST）参与进食、奖赏、厌恶和焦虑样行为。我们鉴定了由囊泡谷氨酸转运体3（VGluT3）表达所定义的BNST神经元。
采用原位杂交、束路追踪、离体全细胞膜片钳电生理学、在体记录、光遗传学和行为学方法相结合。
VGluT3神经元定位于BNST的前内侧，在分子水平上与伏隔核的VGluT3神经元不同，且共表达囊泡GABA转运体（VGaT）。BNST的VGluT3神经元投射到弓状核（ARC）和下丘脑室旁核（PVN），这两个区域对进食和稳态调节至关重要。大多数单个BNST的VGluT3神经元投射到PVN或ARC，一小部分投射到两者。BNST的VGluT3神经元在功能上向ARC和PVN传递GABA，很少向ARC共传递谷氨酸。在体实验中，与禁食时相比，饱腹状态下的VGluT3 BNST神经元在对蔗糖消耗的反应中表现出更高的神经元活性。禁食时，在几种刺激条件下，对BNST的VGluT3神经元进行光遗传学刺激会降低蔗糖消耗，但在蔗糖获取之前进行刺激则不会，这表明在禁食状态下与消耗同时发生的BNST的VGluT3激活会减少进食。在几种范式（新奇抑制进食、旷场实验和高架零迷宫实验）中，BNST的VGluT3激活对焦虑样行为没有影响。BNST的VGluT3激活也不会导致实时位置偏好或厌恶。
我们对这些数据的解释是，VGluT3 BNST神经元代表BNST内一个独特的细胞群体，该群体向下丘脑区域提供抑制性输入以减少蔗糖消耗。
